Leukotriene inhibitors are the first new class of medications for the treatment of persistent asthma that have been approved by the U.S. Food and Drug Administration in more than two decades. They also have been approved for the treatment of allergic rhinitis. Prescriptions of leukotriene inhibitors have outpaced the evidence supporting their use, perhaps because of perceived ease of use compared with other asthma medications. In the treatment of persistent asthma, randomized controlled trials have shown leukotriene inhibitors to be more effective than placebo but less effective than inhaled corticosteroids. The use of leukotriene inhibitors has not consistently shown an inhaled-steroid–sparing effect, a reduction in need for systemic steroid treatment, or a cost savings. For exercise-induced asthma, leukotriene inhibitors are as effective as long-acting beta₂-agonist bronchodilators and are superior to placebo; they have not been compared with short-acting bronchodilators. Leukotriene inhibitors are as effective as antihistamines but are less effective than intranasal steroids for the treatment of allergic rhinitis. The use of leukotriene inhibitors in treating atopic dermatitis, aspirin-intolerant asthma, and chronic idiopathic urticaria appears promising but has not been studied thoroughly. Leukotriene inhibitors have minimal side effects and are well tolerated in most populations. (Am Fam Physician 2007;75:65–70. Copyright © 2007 American Academy of Family Physicians.)